Format

Send to

Choose Destination
BMC Med Imaging. 2019 Sep 18;19(1):78. doi: 10.1186/s12880-019-0375-8.

Development of a novel radioligand for imaging 18-kD translocator protein (TSPO) in a rat model of Parkinson's disease.

Author information

1
Department of Biomedical Imaging and Radiological Science, China Medical University, No.91, Hsueh-Shih Road, Taichung, Taiwan, 40402.
2
Master Program for Biomedical Engineering, China Medical University, No.91, Hsueh-Shih Road, Taichung, Taiwan, 40402.
3
Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, No.155, Sec.2, Linong Street, Taipei, Taiwan, 11221.
4
Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli County, Taiwan, 35053.
5
Department of Biomedical Imaging and Radiological Science, China Medical University, No.91, Hsueh-Shih Road, Taichung, Taiwan, 40402. rancholosamigos@mail.cmuh.org.tw.
6
Graduate Institute of Biomedical Sciences and School of Medicine, College of Medicine, China Medical University, No.91, Hsueh-Shih Road, Taichung, Taiwan, 40402. rancholosamigos@mail.cmuh.org.tw.
7
Graduate Institute of Biomedical Sciences and School of Medicine, College of Medicine, China Medical University, No.91, Hsueh-Shih Road, Taichung, Taiwan, 40402. d10040@mail.cmuh.org.tw.
8
Department of Nuclear Medicine and PET Center, and Center of Augmented Intelligence in Healthcare, China Medical University Hospital, No. 2, Yude Road, North District, Taichung City, Taiwan, 40447. d10040@mail.cmuh.org.tw.
9
Department of Bioinformatics and Medical Engineering, Asia University, 500, Lioufeng Rd., Wufeng, Taichung, Taiwan, 41354. d10040@mail.cmuh.org.tw.

Abstract

PURPOSE:

The inflammation reaction in the brain may stimulate damage repair or possibly lead to secondary brain injury. It is often associated with activated microglia, which would overexpress 18-kDa translocator protein (TSPO). In this study, we successfully developed a new TSPO radioligand, [18F]-2-(4-fluoro-2-(p-tolyloxy)phenyl)-1,2-dihydroisoquinolin-3(4H)-one ([18F]FTPQ), and evaluate its potential to noninvasively detect brain changes in a rat model of Parkinson's disease (PD).

PROCEDURES:

The precursor (8) for [18F]FTPQ preparation was synthesized via six steps. Radiofluorination was carried out in the presence of a copper catalyst, and the crude product was purified by high-performance liquid chromatography (HPLC) to give the desired [18F]FTPQ. The rat model of PD was established by the injection of 6-OHDA into the right hemisphere of male 8-week-old Sprague-Dawley rats. MicroPET/CT imaging and immunohistochemistry (IHC) were performed to characterize the biological properties of [18F]FTPQ.

RESULTS:

The overall chemical yield for the precursor (8) was around 14% after multi-step synthesis. The radiofluorination efficiency of [18F]FTPQ was 60 ± 5%. After HPLC purification, the radiochemical purity was higher than 98%. The overall radiochemical yield was approximately 19%. The microPET/CT images demonstrated apparent striatum accumulation in the brains of PD rats at the first 30 min after intravenous injection of [18F]FTPQ. Besides, longitudinal imaging found the uptake of [18F]FTPQ in the brain may reflect the severity of PD. The radioactivity accumulated in the ipsilateral hemisphere of PD rats at 1, 2, and 3 weeks after 6-OHDA administration was 1.84 ± 0.26, 3.43 ± 0.45, and 5.58 ± 0.72%ID/mL, respectively. IHC revealed that an accumulation of microglia/macrophages and astrocytes in the 6-OHDA-injected hemisphere.

CONCLUSIONS:

In this study, we have successfully synthesized [18F]FTPQ with acceptable radiochemical yield and demonstrated the feasibility of [18F]FTPQ as a TSPO radioligand for the noninvasive monitoring the disease progression of PD.

KEYWORDS:

18-kD translocator protein (TSPO); Parkinson’s disease (PD); Positon emission tomography (PET); [18F]FTPQ

Supplemental Content

Full text links

Icon for BioMed Central Icon for PubMed Central
Loading ...
Support Center